tbuckley/cabot-search huggingface dataset:
Retraction Notice to: Tumor cell-secreted exosomal miR-22-3p inhibits transgelin and induces vascular abnormalization to promote tumor budding
Authors: Yaju Feng, Lumeng Wang, Ting Wang, Ying Li, Qingqing Xun, Renya Zhang, Lin Liu, Lei Li, Wei Wang, Yixuan Tian, Lili Yang, Xiao Zhi, Bijiao Zhou, Xin Chen, Tao Sun, Yanrong Liu
Journal: Molecular Therapy (2022)

(Molecular Therapy 29, 2151–2166; June 2021) This article has been retracted at the request of the editor-in-chief. The editor-in-chief was informed of evidence for image duplication in identical or altered fashion in Figures 3A and 8D, as well as undisclosed reuse of an image in Figure 5B from a previous article in Cell Death & Disease (https://doi.org/10.1038/s41419-018-0902-5), in a PubPeer thread: https://pubpeer.com/publications/F5B591481C516F4CE42C7925AC48E9. Image analysis performed by the journal's editorial office confirmed these findings. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. RETRACTED: Tumor cell-secreted exosomal miR-22-3p inhibits transgelin and induces vascular abnormalization to promote tumor buddingFeng et al.Molecular TherapyFebruary 9, 2021In BriefThis article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). This article has been retracted at the request of the editor-in-chief. The editor-in-chief was informed of evidence for image duplication in identical or altered fashion in Figures 3A and 8D, as well as undisclosed reuse of an image in Figure 5B from a previous article in Cell Death & Disease ( https://doi.org/10.1038/s41419-018-0902-5 ), in a PubPeer thread: https://pubpeer.com/publications/F5B591481C516F4CE42C7925AC48E9 . Full-Text PDF Open Archive
The commercial determinants of health: The mini-budget is a consequence of foundational forces medicine must bear witness to
Authors: Nason Maani, Martin McKee
Journal: BMJ (2022)

<h3>Objectives</h3> Evaluate risk of major adverse cardiovascular events (MACE) with tofacitinib versus tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) with or without a history of atherosclerotic cardiovascular disease (ASCVD) in ORAL Surveillance. <h3>Methods</h3> Patients with RA aged ≥50 years with ≥1 additional CV risk factor received tofacitinib 5 mg or 10 mg two times per day or TNFi. Hazard rations (HRs) were evaluated for the overall population and by history of ASCVD (exploratory analysis). <h3>Results</h3> Risk of MACE, myocardial infarction and sudden cardiac death were increased with tofacitinib versus TNFi in ORAL Surveillance. In patients with history of ASCVD (14.7%; 640/4362), MACE incidence was higher with tofacitinib 5 mg two times per day (8.3%; 17/204) and 10 mg two times per day (7.7%; 17/222) versus TNFi (4.2%; 9/214). HR (combined tofacitinib doses vs TNFi) was 1.98 (95% confidence interval (CI) 0.95 to 4.14; interaction p values: 0.196 (for HR)/0.059 (for incidence rate difference)). In patients without history of ASCVD, MACE HRs for tofacitinib 5 mg two times per day (2.4%; 30/1251) and 10 mg two times per day (2.8%; 34/1234) versus TNFi (2.3%; 28/1237) were, respectively, 1.03 (0.62 to 1.73) and 1.25 (0.76 to 2.07). <h3>Conclusions</h3> This post hoc analysis observed higher MACE risk with tofacitinib versus TNFi in patients with RA and history of ASCVD. Among patients without history of ASCVD, all with prevalent CV risk factors, MACE risk did not appear different with tofacitinib 5 mg two times per day versus TNFi. Due to the exploratory nature of this analysis and low statistical power, we cannot exclude differential MACE risk for tofacitinib 5 mg two times per day versus TNFi among patients without history of ASCVD, but any absolute risk excess is likely low. <h3>Trial registration number</h3> NCT02092467.
Predictors of lung entrapment in malignant pleural effusion
Authors: R. Trovisco, C. Freitas, M. Serino, P. Ferreira, B. Martins, D. Coelho, N. Melo, G. Fernandes, A. Magalhães, H.N. Bastos
Journal: Pulmonology (2022)

Malignant pleural effusion (MPE) is a common complication in advanced stages of malignancy and is associated with poor prognosis. Non-expandable lung (NEL) often occurs and its presence influences the MPE approach. Our main objective was to assess risk factors for malignant NEL. Patients diagnosed with pathologically confirmed MPE between January 2012 and December 2018 in our institution were retrospectively analyzed. Demographic and clinical data of patients were reviewed and compared according to the presence or absence of NEL. A univariate and multivariate binary logistic regression analysis were used to determine predictors of the development of NEL. Of 365 patients included, 68 (18.6%) had NEL. After multivariate analysis, we found that loculated MPE (OR 8.63, 95%CI 4.30-17.33, p<0.001), complete hemithorax opacification (OR 2.81, 95%CI 1.17-6.76, p<0.021), lung cancer (OR 2.09, 95%CI 1.01-4.31, p=0.047) and higher effusion-serum LDH ratio (OR 1.09, 95%CI 1.00-1.17, p=0.039) were independent predictors of malignant NEL. There were no significant differences compared with expandable lung group regarding time from primary malignancy diagnosis to MPE diagnosis (3.0, IQR 0.0-75.8 vs 2.0, IQR 0.0-75.5 weeks, p=0.942) or MPE symptoms onset to MPE diagnosis (4.0, IQR 1.0-9.0 vs 3.0, IQR 1.0-9.0 weeks, p=0.497). Patients with NEL had a higher number of therapeutic pleural drainages (3.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0; p<0.001) and longer hospital stay (32.5, IQR 15.5-46.3 vs 21.0, IQR 11.0-36.0, p=0.007), measured in hospitalization days until the end of life, than patients with expandable lung. The rate of recurrence of pleural effusion was not significantly different between groups (p=0.291). Overall survival (OS) was 3.0 (95%CI, 2.3-3.7) months, regardless of lung expandability (p=0.923). Loculated MPE, complete hemithorax opacification, lung cancer and a higher effusion-serum LDH ratio were found to be independent predictors for NEL. These patients underwent thoracocenteses more frequently and had longer hospitalization days, although without significant impact in the OS.
Increase in Acute Respiratory Illnesses Among Children and Adolescents Associated with Rhinoviruses and Enteroviruses, Including Enterovirus D68 — United States, July–September 2022
Authors: Kevin C. Ma, Amber Winn, Heidi L. Moline, Heather M. Scobie, Claire M. Midgley, Hannah L. Kirking, Jennifer Adjemian, Kathleen P. Hartnett, Dylan Johns, Jefferson M. Jones, Adriana Lopez, Xiaoyan Lu, Ariana Perez, Cria G. Perrine, Andzelika E. Rzucidlo, Meredith L. McMorrow, Benjamin J. Silk, Zachary Stein, Everardo Vega, Aron J. Hall, Leila C. Sahni, Vasanthi Avadhanula, Natasha B. Halasa, Laura S. Stewart, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, New York, Peter G. Szilagyi, Rangaraj Selvarangan, Jennifer E. Schuster, John V. Williams, Marian G. Michaels, Mary A. Staat, Christina Quigley
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Increases in severe respiratory illness and acute flaccid myelitis (AFM) among children and adolescents resulting from enterovirus D68 (EV-D68) infections occurred biennially in the United States during 2014, 2016, and 2018, primarily in late summer and fall. Although EV-D68 annual trends are not fully understood, EV-D68 levels were lower than expected in 2020, potentially because of implementation of COVID-19 mitigation measures (e.g., wearing face masks, enhanced hand hygiene, and physical distancing) (1). In August 2022, clinicians in several geographic areas notified CDC of an increase in hospitalizations of pediatric patients with severe respiratory illness and positive rhinovirus/enterovirus (RV/EV) test results.* Surveillance data were analyzed from multiple national data sources to characterize reported trends in acute respiratory illness (ARI), asthma/reactive airway disease (RAD) exacerbations, and the percentage of positive RV/EV and EV-D68 test results during 2022 compared with previous years. These data demonstrated an increase in emergency department (ED) visits by children and adolescents with ARI and asthma/RAD in late summer 2022. The percentage of positive RV/EV test results in national laboratory-based surveillance and the percentage of positive EV-D68 test results in pediatric sentinel surveillance also increased during this time. Previous increases in EV-D68 respiratory illness have led to substantial resource demands in some hospitals and have also coincided with increases in cases of AFM (2), a rare but serious neurologic disease affecting the spinal cord. Therefore, clinicians should consider AFM in patients with acute flaccid limb weakness, especially after respiratory illness or fever, and ensure prompt hospitalization and referral to specialty care for such cases. Clinicians should also test for poliovirus infection in patients suspected of having AFM because of the clinical similarity to acute flaccid paralysis caused by poliovirus. Ongoing surveillance for EV-D68 is critical to ensuring preparedness for possible future increases in ARI and AFM.
Psychiatrist died by suicide four days after learning of GMC investigation
Authors: Clare Dyer
Journal: BMJ (2022)

More than two centuries ago, Alexander Monro applied some of the principles of physics to the intracranial contents and for the first time hypothesized that the blood circulating in the cranium was of constant volume at all times. This hypothesis was supported by experiments by Kellie. In its original form, the hypothesis had shortcomings that prompted modification by others. What finally came to be known as the Monro–Kellie doctrine, or hypothesis, is that the sum of volumes of brain, CSF, and intracranial blood is constant. An increase in one should cause a decrease in one or both of the remaining two. This hypothesis has substantial theoretical implications in increased intracranial pressure and in decreased CSF volume. Many of the MRI abnormalities seen in intracranial hypotension or CSF volume depletion can be explained by the Monro–Kellie hypothesis. These abnormalities include meningeal enhancement, subdural fluid collections, engorgement of cerebral venous sinuses, prominence of the spinal epidural venous plexus, and enlargement of the pituitary gland.
Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists
Authors: Darren M. Brenner, Lawrence J. Brandt, Marc Fenster, Matthew J. Hamilton, Amrit K. Kamboj, Amy S. Oxentenko, Bruce Wang, William D. Chey
Journal: Clinical Gastroenterology and Hepatology (2022)

Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.
Labour would double the number of medical school places if elected, says shadow chancellor
Authors: Gareth Iacobucci
Journal: BMJ (2022)

The credit spread curve is the difference in spread-versus-Treasuries between long-maturity and short-maturity issues. Two articles published in the 1990s reached opposite conclusions regarding whether the slope of that curve is positive or negative. The authors find that neither study uncovered the essential point that the curve is negatively sloped in most periods but positively sloped in periods of exceptionally low perceived credit risk. The true explanation of the shape of the credit spread curve lies in the shift in valuation metric from spread-versus-Treasuries to price as a percentage of face value as default risk increases. <b>TOPICS:</b>Fixed income and structured finance, statistical methods, credit risk management
GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma
Authors: Tessa Gargett, Lisa M Ebert, Nga T H Truong, Paris M Kollis, Kristyna Sedivakova, Wenbo Yu, Erica C F Yeo, Nicole L Wittwer, Briony L Gliddon, Melinda N Tea, Rebecca Ormsby, Santosh Poonnoose, Jake Nowicki, Orazio Vittorio, David S Ziegler, Stuart M Pitson, Michael P Brown
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but has yet to significantly benefit patients with glioblastoma. Early phase trials of chimeric antigen receptor (CAR) T-cell therapy in patients with glioblastoma have demonstrated that this approach is safe and feasible, but with limited evidence of its effectiveness. The choices of appropriate target antigens for CAR-T-cell therapy also remain limited. Methods We profiled an extensive biobank of patients’ biopsy tissues and patient-derived early passage glioma neural stem cell lines for GD2 expression using immunomicroscopy and flow cytometry. We then employed an approved clinical manufacturing process to make CAR- T cells from patients with peripheral blood of glioblastoma and diffuse midline glioma and characterized their phenotype and function in vitro. Finally, we tested intravenously administered CAR-T cells in an aggressive intracranial xenograft model of glioblastoma and used multicolor flow cytometry, multicolor whole-tissue immunofluorescence and next-generation RNA sequencing to uncover markers associated with effective tumor control. Results Here we show that the tumor-associated antigen GD2 is highly and consistently expressed in primary glioblastoma tissue removed at surgery. Moreover, despite patients with glioblastoma having perturbations in their immune system, highly functional GD2-specific CAR-T cells can be produced from their peripheral T cells using an approved clinical manufacturing process. Finally, after intravenous administration, GD2-CAR-T cells effectively infiltrated the brain and controlled tumor growth in an aggressive orthotopic xenograft model of glioblastoma. Tumor control was further improved using CAR-T cells manufactured with a clinical retroviral vector encoding an interleukin-15 transgene alongside the GD2-specific CAR. These CAR-T cells achieved a striking 50% complete response rate by bioluminescence imaging in established intracranial tumors. Conclusions Targeting GD2 using a clinically deployed CAR-T-cell therapy has a sound scientific and clinical rationale as a treatment for glioblastoma and other aggressive primary brain tumors.
Precision medicine-guided co-delivery of ASPN siRNA and oxaliplatin by nanoparticles to overcome chemoresistance of colorectal cancer
Authors: Cheng-Zhi Huang, Yue Zhou, Qi-Song Tong, Qi-Jia Duan, Qing Zhang, Jin-Zhi Du, Xue-Qing Yao
Journal: Biomaterials (2022)
Widespread false gene gains caused by duplication errors in genome assemblies
Authors: Byung June Ko, Chul Lee, Juwan Kim, Arang Rhie, Dong Ahn Yoo, Kerstin Howe, Jonathan Wood, Seoae Cho, Samara Brown, Giulio Formenti, Erich D. Jarvis, Heebal Kim
Journal: Genome biology (2022)

Abstract Background False duplications in genome assemblies lead to false biological conclusions. We quantified false duplications in popularly used previous genome assemblies for platypus, zebra finch, and Anna’s Hummingbird, and their new counterparts of the same species generated by the Vertebrate Genomes Project, of which the Vertebrate Genomes Project pipeline attempted to eliminate false duplications through haplotype phasing and purging. These assemblies are among the first generated by the Vertebrate Genomes Project where there was a prior chromosomal level reference assembly to compare with. Results Whole genome alignments revealed that 4 to 16% of the sequences are falsely duplicated in the previous assemblies, impacting hundreds to thousands of genes. These lead to overestimated gene family expansions. The main source of the false duplications is heterotype duplications, where the haplotype sequences were relatively more divergent than other parts of the genome leading the assembly algorithms to classify them as separate genes or genomic regions. A minor source is sequencing errors. Ancient ATP nucleotide binding gene families have a higher prevalence of false duplications compared to other gene families. Although present in a smaller proportion, we observe false duplications remaining in the Vertebrate Genomes Project assemblies that can be identified and purged. Conclusions This study highlights the need for more advanced assembly methods that better separate haplotypes and sequence errors, and the need for cautious analyses on gene gains.
CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival
Authors: Camille Danne, Chloé Michaudel, Jurate Skerniskyte, Julien Planchais, Aurélie Magniez, Allison Agus, Marie-Laure Michel, Bruno Lamas, Gregory Da Costa, Madeleine Spatz, Cyriane Oeuvray, Chloé Galbert, Maxime Poirier, Yazhou Wang, Alexia Lapière, Nathalie Rolhion, Tatiana Ledent, Cédric Pionneau, Solenne Chardonnet, Floriant Bellvert, Edern Cahoreau, Amandine Rocher, Rafael Rose Arguello, Carole Peyssonnaux, Sabine Louis, Mathias L Richard, Philippe Langella, Jamel El-Benna, Benoit Marteyn, Harry Sokol
Journal: Gut (2022)

Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown.We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real-time bioenergetic profile analysis (Seahorse).Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction increases mitochondrial reactive oxygen species production leading to the premature death of neutrophilsthrough apoptosis, especially in oxidative environment. The decreased functional neutrophils in tissues might explain the impaired containment of fungi and increased susceptibility to intestinal inflammation.These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.
Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia
Authors: Erin R Shanahan, Seungha Kang, Heidi Staudacher, Ayesha Shah, Anh Do, Grace Burns, Veronique S Chachay, Natasha A Koloski, Simon Keely, Marjorie M Walker, Nicholas J Talley, Mark Morrison, Gerald J Holtmann
Journal: Gut (2022)

Objective Functional dyspepsia (FD) is a complex disorder, with debilitating epigastric symptoms. Evidence suggests alterations in gastrointestinal (GI) motility, visceral hypersensitivity, permeability and low-level immune activation in the duodenum may play a role. However, we still have a relatively poor understanding of how these factors interact to precipitate the onset of FD symptoms which are frequently meal related. The duodenal microbiota, in combination with specific dietary substrates, may be important mediators in disease pathophysiology; however, these interlinked factors have not been thoroughly investigated in FD. Design Eighty-six individuals (56 FD, 30 controls) undergoing endoscopy were consecutively recruited and underwent detailed clinical assessment, including upper GI symptoms, gastric emptying and dietary assessment. Duodenal biopsies were obtained aseptically, and the mucosa-associated microbiota (MAM) analysed via 16S rRNA gene amplicon sequencing. Results The relative abundances of predominant members of the Firmicutes, Bacteroidota and Fusobacteriota phyla were linked to symptom burden in FD. Inverse relationships between the relative abundances of Streptococcus and Prevotella, and the relative abundance of Veillonella spp with gastric emptying time, were also observed. No significant differences in long-term nutrient intake or diet quality were found between FD and controls, and there appeared to be limited association between habitual diet and duodenal MAM profiles. Conclusion This study suggests a link between the duodenal MAM, gastric emptying and FD symptoms, and this is largely independent of long-term dietary intake.
Multi-channel auto-encoders for learning domain invariant representations enabling superior classification of histopathology images
Authors: Andrew Moyes, Richard Gault, Kun Zhang, Ji Ming, Danny Crookes, Jing Wang
Journal: Medical Image Analysis (2022)

Domain shift is a problem commonly encountered when developing automated histopathology pipelines. The performance of machine learning models such as convolutional neural networks within automated histopathology pipelines is often diminished when applying them to novel data domains due to factors arising from differing staining and scanning protocols. The Dual-Channel Auto-Encoder (DCAE) model was previously shown to produce feature representations that are less sensitive to appearance variation introduced by different digital slide scanners. In this work, the Multi-Channel Auto-Encoder (MCAE) model is presented as an extension to DCAE which learns from more than two domains of data. Experimental results show that the MCAE model produces feature representations that are less sensitive to inter-domain variations than the comparative StaNoSA method when tested on a novel synthetic dataset. This was apparent when applying the MCAE, DCAE, and StaNoSA models to three different classification tasks from unseen domains. The results of this experiment show the MCAE model out performs the other models. These results show that the MCAE model is able to generalise better to novel data, including data from unseen domains, than existing approaches by actively learning normalised feature representations.
Reply to Bo Li, Chen Duan, Xiangyang Yao, Xiaoliang Wu, and Hua Xu’s Letter to the Editor re: Christian Fuglesang S. Jensen, Dana A. Ohl, Mikkel Fode, et al. Microdissection Testicular Sperm Extraction Versus Multiple Needle-pass Percutaneous Testicular Sperm Aspiration in Men with Nonobstructive Azoospermia: A Randomized Clinical Trial. Eur Urol. 2022;82:377–384
Authors: Christian Fuglesang S Jensen, Mikkel Fode, Jens Sønksen
Journal: European Urology (2022)
Obinutuzumab, acalabrutinib, and venetoclax, after an optional debulking with bendamustine in relapsed or refractory chronic lymphocytic leukaemia (CLL2-BAAG): a multicentre, open-label, phase 2 trial
Authors: Paula Cramer, Moritz Fürstenau, Sandra Robrecht, Adam Giza, Can Zhang, Anna-Maria Fink, Kirsten Fischer, Petra Langerbeins, Othman Al-Sawaf, Eugen Tausch, Christof Schneider, Johannes Schetelig, Peter Dreger, Sebastian Böttcher, Karl-Anton Kreuzer, Anke Schilhabel, Matthias Ritgen, Monika Brüggemann, Michael Kneba, Stephan Stilgenbauer, Barbara Eichhorst, Michael Hallek
Journal: The Lancet Haematology (2022)